UBP49_HUMAN
ID UBP49_HUMAN Reviewed; 688 AA.
AC Q70CQ1; Q5T3D9; Q5T3E0; Q96CK4;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 49;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 49;
DE AltName: Full=Ubiquitin thioesterase 49;
DE AltName: Full=Ubiquitin-specific-processing protease 49;
GN Name=USP49;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ENZYME ACTIVITY.
RX PubMed=14715245; DOI=10.1016/j.bbrc.2003.12.050;
RA Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S.,
RA Lopez-Otin C.;
RT "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific
RT proteases.";
RL Biochem. Biophys. Res. Commun. 314:54-62(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, IDENTIFICATION IN A
RP COMPLEX WITH RUVBL1 AND PSMC5, AND MUTAGENESIS OF CYS-262.
RX PubMed=23824326; DOI=10.1101/gad.211037.112;
RA Zhang Z., Jones A., Joo H.Y., Zhou D., Cao Y., Chen S.,
RA Erdjument-Bromage H., Renfrow M., He H., Tempst P., Townes T.M.,
RA Giles K.E., Ma L., Wang H.;
RT "USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA
RT splicing.";
RL Genes Dev. 27:1581-1595(2013).
CC -!- FUNCTION: Specifically deubiquitinates histone H2B at 'Lys-120'
CC (H2BK120Ub). H2BK120Ub is a specific tag for epigenetic transcriptional
CC activation and acts as a regulator of mRNA splicing. Deubiquitination
CC is required for efficient cotranscriptional splicing of a large set of
CC exons. {ECO:0000269|PubMed:23824326}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:14715245,
CC ECO:0000269|PubMed:23824326};
CC -!- SUBUNIT: Component of a complex with RUVBL1 and PSMC5.
CC {ECO:0000269|PubMed:23824326}.
CC -!- INTERACTION:
CC Q70CQ1; Q13451: FKBP5; NbExp=2; IntAct=EBI-2511022, EBI-306914;
CC Q70CQ1-2; P43490: NAMPT; NbExp=3; IntAct=EBI-12133829, EBI-2829310;
CC Q70CQ1-2; Q8WV60: PTCD2; NbExp=3; IntAct=EBI-12133829, EBI-12154567;
CC Q70CQ1-2; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-12133829, EBI-10251462;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:23824326}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q70CQ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q70CQ1-2; Sequence=VSP_011556;
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AJ586139; CAE51939.1; -; mRNA.
DR EMBL; AL365205; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04065.1; -; Genomic_DNA.
DR EMBL; BC014176; AAH14176.1; -; mRNA.
DR CCDS; CCDS4861.1; -. [Q70CQ1-2]
DR CCDS; CCDS69111.1; -. [Q70CQ1-1]
DR RefSeq; NP_001273483.1; NM_001286554.1. [Q70CQ1-1]
DR RefSeq; NP_061031.2; NM_018561.4. [Q70CQ1-2]
DR AlphaFoldDB; Q70CQ1; -.
DR BioGRID; 117382; 48.
DR IntAct; Q70CQ1; 51.
DR STRING; 9606.ENSP00000377797; -.
DR MEROPS; C19.073; -.
DR iPTMnet; Q70CQ1; -.
DR PhosphoSitePlus; Q70CQ1; -.
DR BioMuta; USP49; -.
DR DMDM; 52000871; -.
DR jPOST; Q70CQ1; -.
DR MassIVE; Q70CQ1; -.
DR PaxDb; Q70CQ1; -.
DR PeptideAtlas; Q70CQ1; -.
DR PRIDE; Q70CQ1; -.
DR ProteomicsDB; 68519; -. [Q70CQ1-1]
DR ProteomicsDB; 68520; -. [Q70CQ1-2]
DR Antibodypedia; 35153; 112 antibodies from 23 providers.
DR DNASU; 25862; -.
DR Ensembl; ENST00000373006.5; ENSP00000362097.1; ENSG00000164663.15. [Q70CQ1-2]
DR Ensembl; ENST00000394253.7; ENSP00000377797.2; ENSG00000164663.15. [Q70CQ1-1]
DR Ensembl; ENST00000682992.1; ENSP00000507239.1; ENSG00000164663.15. [Q70CQ1-1]
DR GeneID; 25862; -.
DR KEGG; hsa:25862; -.
DR MANE-Select; ENST00000682992.1; ENSP00000507239.1; NM_001286554.2; NP_001273483.1.
DR UCSC; uc003orh.3; human. [Q70CQ1-1]
DR CTD; 25862; -.
DR DisGeNET; 25862; -.
DR GeneCards; USP49; -.
DR HGNC; HGNC:20078; USP49.
DR HPA; ENSG00000164663; Low tissue specificity.
DR neXtProt; NX_Q70CQ1; -.
DR OpenTargets; ENSG00000164663; -.
DR PharmGKB; PA134954570; -.
DR VEuPathDB; HostDB:ENSG00000164663; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00940000157997; -.
DR HOGENOM; CLU_008279_13_1_1; -.
DR InParanoid; Q70CQ1; -.
DR OMA; LWFERSS; -.
DR OrthoDB; 1230415at2759; -.
DR PhylomeDB; Q70CQ1; -.
DR TreeFam; TF315281; -.
DR PathwayCommons; Q70CQ1; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q70CQ1; -.
DR BioGRID-ORCS; 25862; 13 hits in 1123 CRISPR screens.
DR ChiTaRS; USP49; human.
DR GenomeRNAi; 25862; -.
DR Pharos; Q70CQ1; Tbio.
DR PRO; PR:Q70CQ1; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q70CQ1; protein.
DR Bgee; ENSG00000164663; Expressed in buccal mucosa cell and 158 other tissues.
DR ExpressionAtlas; Q70CQ1; baseline and differential.
DR Genevisible; Q70CQ1; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0035616; P:histone H2B conserved C-terminal lysine deubiquitination; IDA:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Hydrolase; Metal-binding;
KW mRNA processing; mRNA splicing; Nucleus; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..688
FT /note="Ubiquitin carboxyl-terminal hydrolase 49"
FT /id="PRO_0000080678"
FT DOMAIN 253..657
FT /note="USP"
FT ZN_FING 2..99
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 169..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..201
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 294..315
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 262
FT /note="Nucleophile"
FT /evidence="ECO:0000305"
FT ACT_SITE 615
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 4
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 6
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 26
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 29
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 41
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 46
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 57
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 63
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 76
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT VAR_SEQ 627..688
FT /note="FWVHCNDSKLNVCSVEEVCKTQAYILFYTQRTVQGNARISETHLQAQVQSSN
FT NDEGRPQTFS -> ACALLCGVGDTERG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011556"
FT MUTAGEN 262
FT /note="C->A: Loss of deubiquitinase activity."
FT /evidence="ECO:0000269|PubMed:23824326"
SQ SEQUENCE 688 AA; 79198 MW; 1DE97A430A636B0B CRC64;
MDRCKHVGRL RLAQDHSILN PQKWCCLECA TTESVWACLK CSHVACGRYI EDHALKHFEE
TGHPLAMEVR DLYVFCYLCK DYVLNDNPEG DLKLLRSSLL AVRGQKQDTP VRRGRTLRSM
ASGEDVVLPQ RAPQGQPQML TALWYRRQRL LARTLRLWFE KSSRGQAKLE QRRQEEALER
KKEEARRRRR EVKRRLLEEL ASTPPRKSAR LLLHTPRDAG PAASRPAALP TSRRVPAATL
KLRRQPAMAP GVTGLRNLGN TCYMNSILQV LSHLQKFREC FLNLDPSKTE HLFPKATNGK
TQLSGKPTNS SATELSLRND RAEACEREGF CWNGRASISR SLELIQNKEP SSKHISLCRE
LHTLFRVMWS GKWALVSPFA MLHSVWSLIP AFRGYDQQDA QEFLCELLHK VQQELESEGT
TRRILIPFSQ RKLTKQVLKV VNTIFHGQLL SQVTCISCNY KSNTIEPFWD LSLEFPERYH
CIEKGFVPLN QTECLLTEML AKFTETEALE GRIYACDQCN SKRRKSNPKP LVLSEARKQL
MIYRLPQVLR LHLKRFRWSG RNHREKIGVH VVFDQVLTME PYCCRDMLSS LDKETFAYDL
SAVVMHHGKG FGSGHYTAYC YNTEGGFWVH CNDSKLNVCS VEEVCKTQAY ILFYTQRTVQ
GNARISETHL QAQVQSSNND EGRPQTFS
